Formaldehyde → HCID 11464145, compound

HRID 491435Notes

Reaction equation

HRID 491435 reaction equation
[N:1]1([CH2:7][CH:8]([C:19]2([OH:23])[CH2:22][CH2:21][CH2:20]2)[C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[CH2:24]=O.O.[OH-].[Na+]>C(O)=O>[CH3:24][N:4]1[CH2:5][CH2:6][N:1]([CH2:7][CH:8]([C:19]2([OH:23])[CH2:22][CH2:21][CH2:20]2)[C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:16])[F:17])[CH:10]=2)[CH2:2][CH2:3]1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 962WaterHCID 14798Sodium HydroxideHCID 11211767HCID 11211767, compound

Product 1

HCID 11464145HCID 11464145, compound

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Conditions

Temperature
70 °C

Procedure

A solution of 1-{2-piperazin-1-yl-1-[3-(trifluoromethyl)phenyl]ethyl}cyclobutanol (60 mg, 0.17 mmol), see Example 14, in formic acid (0.33 mL) at 50° C, was treated with an aqueous solution of formaldehyde (37% in water, 0.14 mL, 0.21 mmol). The reaction was heated at 70° C. for 1.5 h, after which time the reaction was poured into water (5 mL) and basified to pH=10 with the addition of a 2 N aqueous solution of sodium hydroxide. The product was then extracted with ethyl acetate (3×4 mL), and the combined organic extracts were dried over magnesium sulfate and concentrated to yield 1-{2-(4-methylpiperazin-1-yl)-1-[3-(trifluoromethyl)phenyl]ethyl}cyclobutanol as a colorless oil. The product was dissolved in methanol (0.5 mL) and the resulting solution was treated with a saturated methanolic solution of hydrochloric acid (0.5 mL) followed by diethyl ether (2 mL). The solution was stored in the refrigerator for 16 h. The resulting precipitate was filtered and washed with diethyl ether to yield 52 mg (69%) 1-{2-(4-methylpiperazin-1-yl)-1-[3-(trifluoromethyl)phenyl]ethyl}cyclobutanol dihydrochloride as a white solid. MS (ESI) m/z 343 ([M+H]+); HRMS: calcd for C18H25F3N2O.2.00 HCl, 414.1453; found (ESI), 343.2007.

Workup

  1. extractionThe product was then extracted with ethyl acetate (3×4 mL)
  2. dry with materialthe combined organic extracts were dried over magnesium sulfate
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-36ea071a28294f608d5aa597f07b6ad6
Source dataset
uspto-grants-2009_05
Patent number
US07531543B2

Reaction notes

Loading…